8-11758429-A-C

Position:

• chr8-11758429-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001308093.3(GATA4):​c.1286A>C​(p.Asn429Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATA4 NM_001308093.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.05

Genes affected

GATA4 (HGNC:4173): (GATA binding protein 4) This gene encodes a member of the GATA family of zinc-finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes. This protein is thought to regulate genes involved in embryogenesis and in myocardial differentiation and function, and is necessary for normal testicular development. Mutations in this gene have been associated with cardiac septal defects. Additionally, alterations in gene expression have been associated with several cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

GATA4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA4	NM_001308093.3	c.1286A>C	p.Asn429Thr	missense_variant	7/7	ENST00000532059.6	NP_001295022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA4	ENST00000532059.6	c.1286A>C	p.Asn429Thr	missense_variant	7/7	1	NM_001308093.3	ENSP00000435712.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;D;.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Pathogenic	0.52	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Uncertain	2.5	.;M;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.42	N;N;N;.
REVEL	Uncertain	0.62
Sift	Benign	0.092	T;T;T;.
Sift4G	Benign	0.37	T;T;T;T
Polyphen		0.99	.;D;.;.
Vest4		0.49
MutPred		0.53		.;Gain of phosphorylation at S426 (P = 0.1623);.;.;
MVP		0.88
MPC		0.39
ClinPred		0.91	D
GERP RS		4.0
Varity_R		0.057
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs76332456; hg19: chr8-11615938;